Review
Immunology
Sebastian Joyce, Gosife Donald Okoye, John P. Driver
Summary: The large majority of lymphocytes belong to the adaptive immune system, but there are also unconventional lymphocytes that behave more like innate immune cells. These unconventional lymphocytes, called innate/innate-like lymphocytes, can express rearranged antigen receptor genes or not. They integrate sensory signals from the innate immune system and relay them to downstream effector cells, contributing to an appropriate host immune response.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Malgorzata Bajor, Agnieszka Graczyk-Jarzynka, Katsiaryna Marhelava, Anna Burdzinska, Angelika Muchowicz, Agnieszka Goral, Andriy Zhylko, Karolina Soroczynska, Kuba Retecki, Marta Krawczyk, Marta Klopotowska, Zofia Pilch, Leszek Paczek, Karl-Johan Malmberg, Sebastien Walchli, Magdalena Winiarska, Radoslaw Zagozdzon
Summary: This study provides new information on the efficacy of PD-L1-targeted CAR against PD-L1(low) targets. The results show that PD-L1-CAR cells have strong reactivity and cytotoxicity against both PD-L1(high) and PD-L1(low) target cells. Additionally, PD-L1-CAR cells also exhibit potent cytotoxic effects against non-malignant cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Immunology
Margaret R. Dunne, Johannes Wagener, Juergen Loeffler, Derek G. Doherty, Thomas R. Rogers
Summary: This review examines evidence on the human immune response to invasive fungal diseases, with a focus on unconventional lymphocytes such as NK cells, gamma/delta T cells, MAIT cells, iNKT cells, and ILC. Recent discoveries about the roles of these novel lymphocyte groups in antifungal immunity are discussed, and the potential for improving antifungal treatment options through a better understanding of lymphocyte actions is explored.
CLINICAL IMMUNOLOGY
(2021)
Article
Immunology
Jiman Kang, Jedson R. Liggett, Digvijay Patil, Suman Ranjit, Katrina Loh, Anju Duttargi, Yuki Cui, Kesha Oza, Brett S. Frank, DongHyang Kwon, Bhaskar Kallakury, Simon C. Robson, Thomas M. Fishbein, Wanxing Cui, Khalid Khan, Alexander Kroemer
Summary: ILC1 cells play a significant role in fatty liver and ischemia-reperfusion injury under conditions of high-fat diet.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Markus Bo Schoenberg, Xiaokang Li, Xinyu Li, Yongsheng Han, Nikolaus Borner, Dominik Koch, Markus Otto Guba, Jens Werner, Alexandr Bazhin
Summary: This review summarizes the interactions between major immune effector cells and HCC cells to provide new insights for HCC immunotherapy. The studies indicate that CD8(+) T lymphocytes and NK cells can inhibit HCC cells, but HCC cells can also lead to dysfunction of these effector cells through various mechanisms. Innovative approaches like organoids and direct contact cell co-culture are suggested for investigating the interactions and developing novel immunotherapy strategies.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Oncology
Shalu Sharma Kharkwal, Christopher T. Johndrow, Natacha Veerapen, Himanshu Kharkwal, Noemi A. Saavedra-Avila, Leandro J. Carreno, Samantha Rothberg, Jinghang Zhang, Scott J. Garforth, Peter J. Jervis, Lianjun Zhang, Alena Donda, Amareeta K. Besra, Liam R. Cox, Steven C. Almo, Alan Howell, Elizabeth E. Evans, Maurice Zauderer, Gurdyal S. Besra, Steven A. Porcelli
Summary: A novel bispecific T-cell engager (BiTE) was developed to activate iNKT cells for antitumor immunity, enhancing multiple effector functions and promoting tumor-specific CD8(+) cytolytic T-cell responses. Simultaneous checkpoint blockade with anti-CTLA-4 antibodies further enhanced the antitumor effects, providing a potential approach for combination immunotherapy. Multiple injections of covalently stabilized iNKT cell-specific BiTEs led to effective and nontoxic cancer immunotherapy regimens without inducing anergy or exhaustion in responding iNKT cells.
Article
Immunology
Thibault Ghesquiere, Marion Ciudad, Andre Ramon, Helene Greigert, Claire Gerard, Claudie Cladiere, Marine Thebault, Coraline Genet, Herve Devilliers, Francois Maurier, Paul Ornetti, Valerie Quipourt, Pierre-Henry Gabrielle, Catherine Creuzot-Garcher, Georges Tarris, Laurent Martin, Agnes Soudry-Faure, Philippe Saas, Sylvain Audia, Bernard Bonnotte, Maxime Samson
Summary: This study found that MAIT cells in patients with giant cell arteritis (GCA) have differences in cytokine production and proliferation, suggesting that MAIT may play a role in the pathogenesis of GCA.
JOURNAL OF AUTOIMMUNITY
(2021)
Article
Immunology
Xue Wen, Siji Nian, Gang Wei, Pengyuan Kang, Yaqi Yang, Lin Li, Yingchun Ye, Lulu Zhang, Songping Wang, Qing Yuan
Summary: This study evaluated the phenotype and function of circulating mucosal-associated invariant T (MAIT) cells in patients with neutrophilic asthma (NA). The results showed that NA patients had significantly decreased frequency of MAIT cells, altered phenotype, and biased Th17 immune response. The study suggests that MAIT cells could be a potential therapeutic target for NA asthma.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Allergy
Robert Ose, Benno Weigmann, Detlef Schuppan, Ari Waisman, Joachim Saloga, Iris Bellinghausen
Summary: CD56(+)CD3(+) iNKT cells promote allergen-specific gut and lung inflammation in PBMC-engrafted humanized mice, opening up new possibilities for therapeutic intervention in allergic diseases.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Immunology
Xiaoyan Ye, Qing Bao, Hexin Chen, Qingxiang Meng, Qianying Li, Lin Sun, Jian Li, Wenbin Lei, Weiping Wen, Wenjing He, Linyi Jiao, Bixing Fang, Yifang Gao, Chunwei Li
Summary: iNKT cells play a role in the inflammatory subtypes of CRSwNP, with type 2 and type 17 iNKT cells being involved in eosinophilic and neutrophilic inflammation, respectively.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Xiang Li, Chen Jin, Qi Chen, Xihua Zheng, Di Xie, Qielan Wu, Lu Wang, Shiyu Bai, Huimin Zhang, Li Bai
Summary: Invariant NK T (iNKT) cells are enriched in the liver, where a liver-specific CD24(+) iNKT subset with high proliferation and metabolism activity is found but lower granzyme B production. The liver microenvironment also influences the differentiation of conventional T cells, leading to the generation of CD24(+) T cells with different functional characteristics. These findings suggest that the liver microenvironment may induce the generation of a liver-specific iNKT subset that plays a crucial role in maintaining liver homeostasis.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Immunology
Christin Friedrich, Renske L. R. E. Taggenbrock, Remi Doucet-Ladeveze, Gosia Golda, Rebekka Moenius, Panagiota Arampatzi, Natasja A. M. Kragten, Katharina Kreymborg, Mercedes Gomez de Agueero, Wolfgang Kastenmueller, Antoine-Emmanuel Saliba, Dominic Gruen, Klaas P. J. M. van Gisbergen, Georg Gasteiger
Summary: ILC1 cells exhibit similar differentiation pathways in different organs, with a gradual loss of TCF-1 resulting in loss of proliferative potential and increased expression of effector molecules.
Article
Oncology
Louise Rethacker, Maxime Boy, Valeria Bisio, France Roussin, Jordan Denizeau, Anne Vincent-Salomon, Edith Borcoman, Christine Sedlik, Eliane Piaggio, Antoine Toubert, Nicolas Dulphy, Anne Caignard
Summary: Innate lymphoid cells (ILCs), including NK cells and ILC3, play important roles in tissue immune homeostasis and tumor surveillance. In human lymph nodes, NK cells and ILC3s are the prominent subpopulations. However, in tumor-draining lymph nodes and breast cancer tumors, NK cells are more abundant while proportions of ILC3 subsets are low. The local tumor microenvironment inhibits NK cell functions through downregulation of a specific receptor, but cytokine stimulation can restore their functionality.
Article
Multidisciplinary Sciences
Arnika K. Wagner, Nadir Kadri, Chris Tibbitt, Koen van de Ven, Sunitha Bagawath-Singh, Denys Oliinyk, Eric LeGresley, Nicole Campbell, Stephanie Trittel, Peggy Riese, Ulf Ribacke, Tatyana Sandalova, Adnane Achour, Klas Karre, Benedict J. Chambers
Summary: Studies have shown that PD-1 can be expressed on MHC class I-deficient tumor-infiltrating NK cells. The absence of PD-1 alters the phenotype of NK cells and reduces their migration and killing capacity. The expression of PD-1 correlates with CXCR6 and PD-L1 molecules in PD-1-deficient NK cells migrate faster, suggesting cis interactions between PD-1 and PD-L1 on NK cells. These findings suggest a role for the PD-1/PD-L1 axis in tumor-infiltrating NK cells.
Article
Immunology
Yawen Chen, Xianwei Wang, Xiaolei Hao, Bin Li, Wanyin Tao, Shu Zhu, Kun Qu, Haiming Wei, Rui Sun, Hui Peng, Zhigang Tian
Summary: The study reveals the heterogeneity of liver ILC1s and demonstrates the dynamic changes that occur in ILC1 subsets from different origins during ontogeny. Ly49E(+) ILC1s originate from embryonic non-bone marrow hematopoietic progenitor cells and play a role in neonatal innate immunity, while Ly49E(-) ILC1s develop from bone marrow and extramedullary hematopoietic progenitor cells after birth and are involved in adult immune memory responses.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Immunology
Nicholas M. Provine, Ali Amini, Lucy C. Garner, Michael E. B. FitzPatrick, Christina Dold, Laura Silva Reyes, Senthil Chinnakannan, Blanche Oguti, Meriel Raymond, Fulvia Troise, Stefania Capone, Antonella Folgori, Eleanor Barnes, Christine S. Rollier, Andrew J. Pollard, Paul Klenerman
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Yanchun Peng, Suet Ling Felce, Danning Dong, Frank Penkava, Alexander J. Mentzer, Xuan Yao, Guihai Liu, Zixi Yin, Ji-Li Chen, Yongxu Lu, Dannielle Wellington, Peter A. C. Wing, Delaney C. C. Dominey-Foy, Chen Jin, Wenbo Wang, Megat Abd Hamid, Ricardo A. Fernandes, Beibei Wang, Anastasia Fries, Xiaodong Zhuang, Neil Ashley, Timothy Rostron, Craig Waugh, Paul Sopp, Philip Hublitz, Ryan Beveridge, Tiong Kit Tan, Christina Dold, Andrew J. Kwok, Charlotte Rich-Griffin, Wanwisa Dejnirattisa, Chang Liu, Prathiba Kurupati, Isar Nassiri, Robert A. Watson, Orion Tong, Chelsea A. Taylor, Piyush Kumar Sharma, Bo Sun, Fabiola Curion, Santiago Revale, Lucy C. Garner, Kathrin Jansen, Ricardo C. Ferreira, Moustafa Attar, Jeremy W. Fry, Rebecca A. Russell, Hans J. Stauss, William James, Alain Townsend, Ling-Pei Ho, Paul Klenerman, Juthathip Mongkolsapaya, Gavin R. Screaton, Calliope Dendrou, Stephen N. Sansom, Rachael Bashford-Rogers, Benny Chain, Geoffrey L. Smith, Jane A. McKeating, Benjamin P. Fairfax, Paul Bowness, Andrew J. McMichael, Graham Ogg, Julian C. Knight, Tao Dong
Summary: Specific CD8(+) T cell responses targeting NP105-113-B*07:02 are associated with mild COVID-19 disease and high antiviral efficacy, providing potential targets for T cell vaccine design. These T cell responses show long-lasting preservation of antiviral functionality post-infection.
Article
Medicine, Research & Experimental
Hannah R. Sharpe, Nicholas M. Provine, Georgina S. Bowyer, Pedro Moreira Folegatti, Sandra Belij-Rammerstorfer, Amy Flaxman, Rebecca Makinson, Adrian Vs Hill, Katie J. Ewer, Andrew J. Pollard, Paul Klenerman, Sarah Gilbert, Teresa Lambe
Summary: This study found that cytomegalovirus (CMV) infection does not affect antigen-specific T cell interferon-gamma secretion or antibody IgG production after vaccination, which has important implications for the widespread use of this vaccine, particularly in low- and middle-income countries with high CMV seroprevalence.
Article
Biochemistry & Molecular Biology
David J. Ahern, Zhichao Ai, Mark Ainsworth, Chris Allan, Alice Allcock, Brian Angus, M. Azim Ansari, Carolina Arancibia-Carcamo, Dominik Aschenbrenner, Moustafa Attar, J. Kenneth Baillie, Eleanor Barnes, Rachael Bashford-Rogers, Archana Bashyal, Sally Beer, Georgina Berridge, Amy Beveridge, Sagida Bibi, Tihana Bicanic, Luke Blackwell, Paul Bowness, Andrew Brent, Andrew Brown, John Broxholme, David Buck, Katie L. Burnham, Helen Byrne, Susana Camara, Ivan Candido Ferreira, Philip Charles, Wentao Chen, Yi-Ling Chen, Amanda Chong, Elizabeth A. Clutterbuck, Mark Coles, Christopher P. Conlon, Richard Cornall, Adam P. Cribbs, Fabiola Curion, Emma E. Davenport, Neil Davidson, Simon Davis, Calliope A. Dendrou, Julie Dequaire, Lea Dib, James Docker, Christina Dold, Tao Dong, Damien Downes, Hal Drakesmith, Susanna J. Dunachie, David A. Duncan, Chris Eijsbouts, Robert Esnouf, Alexis Espinosa, Rachel Etherington, Benjamin Fairfax, Rory Fairhead, Hai Fang, Shayan Fassih, Sally Felle, Maria Fernandez Mendoza, Ricardo Ferreira, Roman Fischer, Thomas Foord, Aden Forrow, John Frater, Anastasia Fries, Veronica Gallardo Sanchez, Lucy C. Garner, Clementine Geeves, Dominique Georgiou, Leila Godfrey, Tanya Golubchik, Maria Gomez Vazquez, Angie Green, Hong Harper, Heather A. Harrington, Raphael Heilig, Svenja Hester, Jennifer Hill, Charles Hinds, Clare Hird, Ling-Pei Ho, Renee Hoekzema, Benjamin Hollis, Jim Hughes, Paula Hutton, Matthew A. Jackson-Wood, Ashwin Jainarayanan, Anna James-Bott, Kathrin Jansen, Katie Jeffery, Elizabeth Jones, Luke Jostins, Georgina Kerr, David Kim, Paul Klenerman, Julian C. Knight, Vinod Kumar, Piyush Kumar Sharma, Prathiba Kurupati, Andrew Kwok, Angela Lee, Aline Linder, Teresa Lockett, Lorne Lonie, Maria Lopopolo, Martyna Lukoseviciute, Jian Luo, Spyridoula Marinou, Brian Marsden, Jose Martinez, Philippa C. Matthews, Michalina Mazurczyk, Simon McGowan, Stuart McKechnie, Adam Mead, Alexander J. Mentzer, Yuxin Mi, Claudia Monaco, Ruddy Montadon, Giorgio Napolitani, Isar Nassiri, Alex Novak, Darragh P. O'Brien, Daniel O'Connor, Denise O'Donnell, Graham Ogg, Lauren Overend, Inhye Park, Ian Pavord, Yanchun Peng, Frank Penkava, Mariana Pereira Pinho, Elena Perez, Andrew J. Pollard, Fiona Powrie, Bethan Psaila, T. Phuong Quan, Emmanouela Repapi, Santiago Revale, Laura Silva-Reyes, Jean-Baptiste Richard, Charlotte Rich-Griffin, Thomas Ritter, Christine S. Rollier, Matthew Rowland, Fabian Ruehle, Mariolina Salio, Stephen Nicholas Sansom, Raphael Sanches Peres, Alberto Santos Delgado, Tatjana Sauka-Spengler, Ron Schwessinger, Giuseppe Scozzafava, Gavin Screaton, Anna Seigal, Malcolm G. Semple, Martin Sergeant, Christina Simoglou Karali, David Sims, Donal Skelly, Hubert Slawinski, Alberto Sobrinodiaz, Nikolaos Sousos, Lizzie Stafford, Lisa Stockdale, Marie Strickland, Otto Sumray, Bo Sun, Chelsea Taylor, Stephen Taylor, Adan Taylor, Supat Thongjuea, Hannah Thraves, John A. Todd, Adriana Tomic, Orion Tong, Amy Trebes, Dominik Trzupek, Felicia Anna Tucci, Lance Turtle, Irina Udalova, Holm Uhlig, Erinke van Grinsven, Iolanda Vendrell, Marije Verheul, Alexandru Voda, Guanlin Wang, Lihui Wang, Dapeng Wang, Peter Watkinson, Robert Watson, Michael Weinberger, Justin Whalley, Lorna Witty, Katherine Wray, Luzheng Xue, Hing Yuen Yeung, Zixi Yin, Rebecca K. Young, Jonathan Youngs, Ping Zhang, Yasemin-Xiomara Zurke
Summary: The study presents a comprehensive blood atlas for patients with varying severity of COVID-19, compared to influenza, sepsis patients, and healthy volunteers. The results identify immune signatures and correlates of host response, including cells, inflammatory mediators, immune repertoire, and metabolic and coagulation features. The study also reveals that persistent immune activation is a specific feature of COVID-19. Plasma proteomic analysis enables sub-phenotyping and prediction of severity and outcome. Integrative analyses show feature groupings linked with severity and specificity compared to influenza and sepsis.
Review
Immunology
Hema Mehta, Martin Joseph Lett, Paul Klenerman, Magdalena Filipowicz Sinnreich
Summary: MAIT cells are a unique subset of T lymphocytes abundant in humans, especially in the liver, that bridge innate and adaptive immunity by responding to bacterial metabolites presented by MR1. They possess a wide array of cytokine receptors, enabling them to respond independently of TCR. This distinctive cell type plays a role not only in infection or inflammation, but also in maintaining homeostasis and could have therapeutic implications in liver diseases.
SEMINARS IN IMMUNOPATHOLOGY
(2022)
Correction
Immunology
Hema Mehta, Martin Joseph Lett, Paul Klenerman, Magdalena Filipowicz Sinnreich
SEMINARS IN IMMUNOPATHOLOGY
(2022)
Review
Immunology
Nicholas M. M. Provine, Paul Klenerman
Summary: Replication-incompetent adenovirus vector and mRNA-lipid nanoparticle constructs are two modular vaccine platforms that have gained substantial interest. The COVID-19 pandemic and successful vaccines based on these technologies have provided real-world evidence of their utility. Despite optimization efforts, our understanding of the specific mechanisms by which these vaccines stimulate the immune response remains incomplete.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Cell Biology
Hema Mehta, Irene Tasin, Carl Philipp Hackstein, Christian Willberg, Paul Klenerman
Summary: Mucosal-associated invariant T (MAIT) cells are a type of innate-like T-cell that is conserved in many mammals and abundant in humans. They have a semi-invariant T-cell receptor (TCR) that recognizes riboflavin intermediates associated with microbial metabolism. MAIT cell activation can be triggered by cytokines and is highly sensitive to local soluble mediators. Prostaglandins can potentially modulate the functions of MAIT cells in vivo, with distinct effects on TCR-dependent and TCR-independent pathways of activation.
IMMUNOLOGY AND CELL BIOLOGY
(2023)
Editorial Material
Cell Biology
Prabhjeet Phalora, Paul Klenerman
JOURNAL OF CELL BIOLOGY
(2022)
Review
Immunology
Carl-Philipp Hackstein, Paul Klenerman
Summary: T cells can recognize conventional or unconventional ligands and exhibit innate-like features and independent responses in an antigen-dependent or -independent manner. Unconventional T cells, such as MAIT cells, show innate-like features and respond independently of their T cell receptors (TCRs), while conventional T cells, such as T(MIC) cells, also exhibit innate-like behavior. The abilities to recognize antigens presented by unconventional antigen-presenting molecules or to mount TCR-independent responses create unique niches for these T cells.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Wojciech Barczak, Simon M. M. Carr, Geng Liu, Shonagh Munro, Annalisa Nicastri, Lian Ni Lee, Claire Hutchings, Nicola Ternette, Paul Klenerman, Alexander Kanapin, Anastasia Samsonova, Nicholas B. B. La Thangue
Summary: PRMT5, an over-expressed protein arginine methyltransferase (PRMT) in various cancers, plays a role in regulating the non-coding genome by affecting long non-coding (lnc) RNA gene expression. Additionally, inhibiting PRMT5 or adjusting E2F1 levels alters the repertoire of lncRNA-derived peptide antigens displayed by tumor cells and lncRNA-derived peptides can induce a potent antigen-specific CD8 T lymphocyte response when used as a cancer vaccine.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Juan Carlos Lopez-Rodriguez, Steven J. Hancock, Kelin Li, Stefania Crotta, Christopher Barrington, Alejandro Suarez-Bonnet, Simon L. Priestnall, Jeffrey Aube, Andreas Wack, Paul Klenerman, Jose A. Bengoechea, Patricia Barral
Summary: Mucosal-associated invariant T (MAIT) cells in the lungs are important for host defense against infections. This study demonstrates that MAIT cell activation during bacterial pneumonia caused by Klebsiella pneumoniae is independent of MR1 and driven by type I interferons (IFNs). Type I IFNs stimulate the activation and effector functions of MAIT cells and play a central role in their response to Klebsiella infection. This finding suggests that targeting type I IFNs could be a strategy to manipulate MAIT cell functions during bacterial infections.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Immunology
Lucy C. Garner, Ali Amini, Michael E. B. FitzPatrick, Martin J. Lett, Gabriel F. Hess, Magdalena Filipowicz Sinnreich, Nicholas M. Provine, Paul Klenerman
Summary: Garner et al. analyzed the single-cell transcriptome and TCR repertoire of matched blood and liver, and resting and activated, human MAIT cells. They identify donor-specific TCR repertoires shared across tissues and a transcriptome that is largely homogeneous at rest, but highly adaptive to different tissue and stimulation environments.